This article was downloaded by: [University of Louisville] On: 04 February 2015, At: 23:06 Publisher: Routledge Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
The American Journal of Bioethics Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/uajb20
Empirical Ethics: The “Missing Link” in Incidental Findings Recommendations a
a
Gabrielle Christenhusz , Koenraad Devriendt & Kris Dierickx
a
a
KU Leuven Published online: 04 Mar 2014.
Click for updates To cite this article: Gabrielle Christenhusz , Koenraad Devriendt & Kris Dierickx (2014) Empirical Ethics: The “Missing Link” in Incidental Findings Recommendations, The American Journal of Bioethics, 14:3, 31-33, DOI: 10.1080/15265161.2013.879949 To link to this article: http://dx.doi.org/10.1080/15265161.2013.879949
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
Genetic Testing and Sequencing of Children
Incidental findings in clinical genomics: A clarification. 2013. Genetics in Medicine 15(8): 664–66. Levy, D., G. L. Splansky, N. K. Strand, et al. 2010. Consent for genetic research in the Framingham Heart Study. American Journal of Medical Genetics 152A(5): 1250–1256. Nelson, H. D., M. Pappas, B. Zakher, J. P. Mitchell, L. OkinakaHu, and R. Fu. 2013. Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: A systemataic review to update the U.S. Preventive Services Task Force recommendation. Annals of Internal Medicine. Available at: http://www. uspreventiveservicetaskforce.org/uspstf12/brcatest/brcatestart. pdf
Downloaded by [University of Louisville] at 23:06 04 February 2015
Robins Wahlin, T. B. 2007. To know or not to know: A review of behaviour and suicidal ideation in preclinical Huntington’s disease. Patient Education and Counseling 2007;65(3): 279–287.
Ross, L. F., H. M. Saal, K. L. David, et al. 2013. Technical report: Ethical and policy issues in genetic testing and screening of children. Genetics in Medicine 15(3): 234–245. Tassicker, R. J., B. Teltscher, M. K. Trembath, et al. 2009. Problems assessing uptake of Huntington disease predictive testing and a proposed solution. European Journal of Human Genetics 17:66– 70. Tibben, A. 2007. Predictive testing for Huntington’s disease. Brain Res. Bull. 72:165–171. Van Oostrom, I., and A. Tibben. 2004. A counselling model for BRCA1/2 genetic susceptibility testing. Hereditary Cancer in Clinical Practice 2:19–23. Wolf, S. M., G. J. Annas, and S. Elias. 2013. Patient autonomy and incidental findings in clinical genomics. Science 340:1049– 1050.
Empirical Ethics: The “Missing Link” in Incidental Findings Recommendations Gabrielle Christenhusz, KU Leuven Koenraad Devriendt, KU Leuven Kris Dierickx, KU Leuven While Clayton and colleagues (2014) rightly highlight the differences and tensions in the ethical justifications utilized by what they refer to as the American Academy of Pediatrics (AAP)/American College of Medical Genetics and Genomics (ACMG) and ACMG exome sequencing/genome sequencing (ES/GS) recommendations, they fall short in explaining the source of these differences. Only once the source of the differences is correctly identified and explored can the implications of tensions between the two sets of recommendations be addressed: that is, whether or not they need to agree. We argue that the differences largely rest on the implied methodologies underlying the two guidelines. The AAP/ACMG recommendations make use of the results of empirical ethics involving a range of stakeholders, a methodology that the ACMG ES/GS guideline ignores. Clayton and colleagues describe how the former recommendations on predictive genetic testing and screening of children situate themselves within the professional tradition and empirical research on how adults and families respond to predictive testing. The latter recommendations, in contrast, make no reference to either this professional tradition
or empirical research in justifying their position. These recommendations appear to have been inspired mainly by the views of some medical professionals, without taking into account all the other stakeholders who will be impacted by the guidelines. This lacuna severely weakens the persuasiveness of the ACMG ES/GS recommendations. So-called “empirical ethics” involves bringing general principles and particular judgments or experiences into conversation with each other, with the aim of advancing in ethical reflection (Schotsmans 1999). Neither the normative nor the empirical should be given undue weight, but both should be allowed to inform and challenge each other. A prerequisite is an accurate description of the context (Borry, Schotsmans, and Dierickx 2004). The context of the AAP/ACMG recommendations is a positive family history, in which both children and adults will know that they can choose to request testing once they are over majority. The ACMG ES/GS recommendations assume no positive family history. Consequently, the disclosure of an incidental finding discovered in the child is the only way that the rest of the family members will know that they might want to get tested. (Incidentally, if a positive family history were
Address correspondence to Gabrielle Christenhusz, KU Leuven, Centre for Biomedical Ethics and Law, Kapucijnenvoer 35/3, Leuven 300, Belgium. E-mail: [email protected]
March, Volume 14, Number 3, 2014
ajob 31
Downloaded by [University of Louisville] at 23:06 04 February 2015
The American Journal of Bioethics
to be present, the context reverts to one similar to that of the AAP/ACMG recommendations; this would only come to light if clinicians and laboratory staff were in communication about the patients, a possibility that does not seem to be explored in the present guidelines.) Other aspects of the context remain to be specified. For instance, are we to assume the current situation, where ES/GS is mainly ordered for children in cases of serious developmental disabilities or congenital anomalies; that is, in cases where the family already has to deal with a severe clinical condition? There is additionally the justice and practical question of who will finance the extra laboratory workup. It will be helpful to get some idea of the scale of impact of the guidelines, by looking, for instance, at the expected proportion of actionable, pathogenic incidental findings based on current, admittedly limited databases (e.g., Dorschner et al. 2013), and by clarifying how far investigations of relatives should go to determine the clinical significance of a suspected incidental finding (Crawford et al. 2013). Ethically sound guidelines should also keep in mind the consequences at each step of the disclosure process: from laboratory to clinician, from clinician to parents, and, perhaps most crucially, from parents to children. Once the context has been delimited in as detailed a way as possible, normative and empirical explorations can be brought into the conversation. While there are numerous guidelines and normative position papers arguing against predictive testing of children for adult-onset disorders, which the AAP/ACMG recommendations make use of, there are other arguments encouraging early predictive testing (Rhodes 2006). The accompanying technical report of the AAP/ACMG allows for exceptions depending on the family’s motivation, context, and understanding. The question is whether the exception can ever become the rule. The ACMG ES/GS recommendations take the family as the basic unit of clinical care, rather than the child. Some recent clinical literature supports viewing incidental findings in children of adult-onset conditions as family matters (May, Zusevics, and Strong 2013). Another relevant line of inquiry is whether the so-called “right not to know” that some parents or children (or future adult children) may wish to claim is valid in the case of actionable, pathogenic incidental findings. Naysayers include those who argue that such ignorance can be harmful, those who argue that such ignorance is opposed to autonomy, and those who argue that the discussion should move to harms and benefits at an intersubjective level (Wilson 2005). The normative ethical work is yet to be done, not just to shore up arguments defending the ACMG’s latest position but also to justify the apparent radical break with former recommendations. Helpful in this process are empirical investigations of the values and motivations relevant to stakeholders in the context of pediatric genetic incidental findings. Stakeholders include medical professionals, laboratory personnel, parents, families, and children (if possible). Such investigations can clarify the weighting of various norma-
32 ajob
tive positions. In this respect, it is not enough simply to know whether parents for instance would accept the consequences of the ACMG ES/GS recommendations, but one needs to also know their reasons for doing so. Two recent comparable interview studies suggest that most parents would appreciate the disclosure of adult-onset, actionable, pathogenic incidental findings discovered in their children (Christenhusz et al. in press; Sapp et al. 2013). More interesting from an ethical point of view is how parents justified their positions, as well as the sorts of justifications used by those opposed to disclosure, and the ethical weight that can be ascribed to each type of argument. Also interesting is our finding that some of those who said that they did not want certain results disclosed to them found it unacceptable that the doctor know something about their child that they did not (Christenhusz et al. in press). In other words, they would rather forgo their “right not to know” than have the doctor know a certain unexpected result and not disclose it. A finding like this deserves more investigation. One response is that medical professionals should be very sure about what they want to discover about their patients; after all, what they do not know themselves, they cannot disclose. We have argued that the main difference between the AAP/ACMG and ACMG ES/GS recommendations lies in the “missing link” of empirical ethics, and have attempted to show how normative ethical reflections and empirical investigations could be brought together to flesh out the ACMG ES/GS recommendations. If it can be shown that different ethical arguments are valid for the two sets of recommendations, based on justifiably different contexts, it can then be argued that these evolving, ethically sound, internally consistent guidelines need not agree with each other.
REFERENCES Borry, P., S. Schotsmans, and K. Dierickx. 2004. What is the role of empirical research in bioethical reflection and decision-making? An ethical analysis. Medicine, Health Care and Philosophy 7: 41–53. Christenhusz, G. M., K. Devriendt, H. Peters, H. Van Esch, and K. Dierickx. In press. The communication of secondary variants: Interviews with parents whose children have undergone arrayCGH testing. Clayton, E. W., L. B. McCullough, L.G. Biessecker, S. Joffe, L. F. Ross, and S. M. Wolf. 2014. Addressing the ethical challenges in genetic testing and sequencing of children. American Journal of Bioethics 14(3): 3–9. Crawford, G., N. Foulds, A. Fenwick, N. Hallowell, and A. Lucassen. 2013. Genetic medicine and incidental findings: It is more complicated than deciding whether to disclose or not. Genetics in Medicine 15: 896–899. Dorschner, M. O., L. M. Amendola, E. H. Turner, et al. 2013. Actionable, pathogenic incidental findings in 1,000 participants’ exomes. American Journal of Human Genetics 93(4): 631–640.
March, Volume 14, Number 3, 2014
Genetic Testing and Sequencing of Children
May, T., K. L. Zusevics, and K. A. Strong. 2013. On the ethics of clinical whole genome sequencing of children. Pediatrics. Epub ahead of print. doi: 10.1542/peds.2012-3788. Rhodes, R. 2006. Why test children for adult-onset genetic diseases? Mount Sinai Journal of Medicine 73:609–616.
Schotsmans, P. 1999. Personalism in medical ethics. Ethical Perspectives 6(1): 10–20. Wilson, J. 2005. To know or not to know? Genetic ignorance, autonomy and paternalism. Bioethics 19:492–504.
Downloaded by [University of Louisville] at 23:06 04 February 2015
Sapp, J. C., D. Dong, C. Stark, et al. 2013. Parental attitudes, values, and beliefs toward the return of results from exome se-
quencing in children. Clinical Genetics. Epub ahead of print. doi: 10.1111/cge.12254.
March, Volume 14, Number 3, 2014
ajob 33
The American Journal of Bioethics Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/uajb20
Empirical Ethics: The “Missing Link” in Incidental Findings Recommendations a
a
Gabrielle Christenhusz , Koenraad Devriendt & Kris Dierickx
a
a
KU Leuven Published online: 04 Mar 2014.
Click for updates To cite this article: Gabrielle Christenhusz , Koenraad Devriendt & Kris Dierickx (2014) Empirical Ethics: The “Missing Link” in Incidental Findings Recommendations, The American Journal of Bioethics, 14:3, 31-33, DOI: 10.1080/15265161.2013.879949 To link to this article: http://dx.doi.org/10.1080/15265161.2013.879949
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
Genetic Testing and Sequencing of Children
Incidental findings in clinical genomics: A clarification. 2013. Genetics in Medicine 15(8): 664–66. Levy, D., G. L. Splansky, N. K. Strand, et al. 2010. Consent for genetic research in the Framingham Heart Study. American Journal of Medical Genetics 152A(5): 1250–1256. Nelson, H. D., M. Pappas, B. Zakher, J. P. Mitchell, L. OkinakaHu, and R. Fu. 2013. Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: A systemataic review to update the U.S. Preventive Services Task Force recommendation. Annals of Internal Medicine. Available at: http://www. uspreventiveservicetaskforce.org/uspstf12/brcatest/brcatestart. pdf
Downloaded by [University of Louisville] at 23:06 04 February 2015
Robins Wahlin, T. B. 2007. To know or not to know: A review of behaviour and suicidal ideation in preclinical Huntington’s disease. Patient Education and Counseling 2007;65(3): 279–287.
Ross, L. F., H. M. Saal, K. L. David, et al. 2013. Technical report: Ethical and policy issues in genetic testing and screening of children. Genetics in Medicine 15(3): 234–245. Tassicker, R. J., B. Teltscher, M. K. Trembath, et al. 2009. Problems assessing uptake of Huntington disease predictive testing and a proposed solution. European Journal of Human Genetics 17:66– 70. Tibben, A. 2007. Predictive testing for Huntington’s disease. Brain Res. Bull. 72:165–171. Van Oostrom, I., and A. Tibben. 2004. A counselling model for BRCA1/2 genetic susceptibility testing. Hereditary Cancer in Clinical Practice 2:19–23. Wolf, S. M., G. J. Annas, and S. Elias. 2013. Patient autonomy and incidental findings in clinical genomics. Science 340:1049– 1050.
Empirical Ethics: The “Missing Link” in Incidental Findings Recommendations Gabrielle Christenhusz, KU Leuven Koenraad Devriendt, KU Leuven Kris Dierickx, KU Leuven While Clayton and colleagues (2014) rightly highlight the differences and tensions in the ethical justifications utilized by what they refer to as the American Academy of Pediatrics (AAP)/American College of Medical Genetics and Genomics (ACMG) and ACMG exome sequencing/genome sequencing (ES/GS) recommendations, they fall short in explaining the source of these differences. Only once the source of the differences is correctly identified and explored can the implications of tensions between the two sets of recommendations be addressed: that is, whether or not they need to agree. We argue that the differences largely rest on the implied methodologies underlying the two guidelines. The AAP/ACMG recommendations make use of the results of empirical ethics involving a range of stakeholders, a methodology that the ACMG ES/GS guideline ignores. Clayton and colleagues describe how the former recommendations on predictive genetic testing and screening of children situate themselves within the professional tradition and empirical research on how adults and families respond to predictive testing. The latter recommendations, in contrast, make no reference to either this professional tradition
or empirical research in justifying their position. These recommendations appear to have been inspired mainly by the views of some medical professionals, without taking into account all the other stakeholders who will be impacted by the guidelines. This lacuna severely weakens the persuasiveness of the ACMG ES/GS recommendations. So-called “empirical ethics” involves bringing general principles and particular judgments or experiences into conversation with each other, with the aim of advancing in ethical reflection (Schotsmans 1999). Neither the normative nor the empirical should be given undue weight, but both should be allowed to inform and challenge each other. A prerequisite is an accurate description of the context (Borry, Schotsmans, and Dierickx 2004). The context of the AAP/ACMG recommendations is a positive family history, in which both children and adults will know that they can choose to request testing once they are over majority. The ACMG ES/GS recommendations assume no positive family history. Consequently, the disclosure of an incidental finding discovered in the child is the only way that the rest of the family members will know that they might want to get tested. (Incidentally, if a positive family history were
Address correspondence to Gabrielle Christenhusz, KU Leuven, Centre for Biomedical Ethics and Law, Kapucijnenvoer 35/3, Leuven 300, Belgium. E-mail: [email protected]
March, Volume 14, Number 3, 2014
ajob 31
Downloaded by [University of Louisville] at 23:06 04 February 2015
The American Journal of Bioethics
to be present, the context reverts to one similar to that of the AAP/ACMG recommendations; this would only come to light if clinicians and laboratory staff were in communication about the patients, a possibility that does not seem to be explored in the present guidelines.) Other aspects of the context remain to be specified. For instance, are we to assume the current situation, where ES/GS is mainly ordered for children in cases of serious developmental disabilities or congenital anomalies; that is, in cases where the family already has to deal with a severe clinical condition? There is additionally the justice and practical question of who will finance the extra laboratory workup. It will be helpful to get some idea of the scale of impact of the guidelines, by looking, for instance, at the expected proportion of actionable, pathogenic incidental findings based on current, admittedly limited databases (e.g., Dorschner et al. 2013), and by clarifying how far investigations of relatives should go to determine the clinical significance of a suspected incidental finding (Crawford et al. 2013). Ethically sound guidelines should also keep in mind the consequences at each step of the disclosure process: from laboratory to clinician, from clinician to parents, and, perhaps most crucially, from parents to children. Once the context has been delimited in as detailed a way as possible, normative and empirical explorations can be brought into the conversation. While there are numerous guidelines and normative position papers arguing against predictive testing of children for adult-onset disorders, which the AAP/ACMG recommendations make use of, there are other arguments encouraging early predictive testing (Rhodes 2006). The accompanying technical report of the AAP/ACMG allows for exceptions depending on the family’s motivation, context, and understanding. The question is whether the exception can ever become the rule. The ACMG ES/GS recommendations take the family as the basic unit of clinical care, rather than the child. Some recent clinical literature supports viewing incidental findings in children of adult-onset conditions as family matters (May, Zusevics, and Strong 2013). Another relevant line of inquiry is whether the so-called “right not to know” that some parents or children (or future adult children) may wish to claim is valid in the case of actionable, pathogenic incidental findings. Naysayers include those who argue that such ignorance can be harmful, those who argue that such ignorance is opposed to autonomy, and those who argue that the discussion should move to harms and benefits at an intersubjective level (Wilson 2005). The normative ethical work is yet to be done, not just to shore up arguments defending the ACMG’s latest position but also to justify the apparent radical break with former recommendations. Helpful in this process are empirical investigations of the values and motivations relevant to stakeholders in the context of pediatric genetic incidental findings. Stakeholders include medical professionals, laboratory personnel, parents, families, and children (if possible). Such investigations can clarify the weighting of various norma-
32 ajob
tive positions. In this respect, it is not enough simply to know whether parents for instance would accept the consequences of the ACMG ES/GS recommendations, but one needs to also know their reasons for doing so. Two recent comparable interview studies suggest that most parents would appreciate the disclosure of adult-onset, actionable, pathogenic incidental findings discovered in their children (Christenhusz et al. in press; Sapp et al. 2013). More interesting from an ethical point of view is how parents justified their positions, as well as the sorts of justifications used by those opposed to disclosure, and the ethical weight that can be ascribed to each type of argument. Also interesting is our finding that some of those who said that they did not want certain results disclosed to them found it unacceptable that the doctor know something about their child that they did not (Christenhusz et al. in press). In other words, they would rather forgo their “right not to know” than have the doctor know a certain unexpected result and not disclose it. A finding like this deserves more investigation. One response is that medical professionals should be very sure about what they want to discover about their patients; after all, what they do not know themselves, they cannot disclose. We have argued that the main difference between the AAP/ACMG and ACMG ES/GS recommendations lies in the “missing link” of empirical ethics, and have attempted to show how normative ethical reflections and empirical investigations could be brought together to flesh out the ACMG ES/GS recommendations. If it can be shown that different ethical arguments are valid for the two sets of recommendations, based on justifiably different contexts, it can then be argued that these evolving, ethically sound, internally consistent guidelines need not agree with each other.
REFERENCES Borry, P., S. Schotsmans, and K. Dierickx. 2004. What is the role of empirical research in bioethical reflection and decision-making? An ethical analysis. Medicine, Health Care and Philosophy 7: 41–53. Christenhusz, G. M., K. Devriendt, H. Peters, H. Van Esch, and K. Dierickx. In press. The communication of secondary variants: Interviews with parents whose children have undergone arrayCGH testing. Clayton, E. W., L. B. McCullough, L.G. Biessecker, S. Joffe, L. F. Ross, and S. M. Wolf. 2014. Addressing the ethical challenges in genetic testing and sequencing of children. American Journal of Bioethics 14(3): 3–9. Crawford, G., N. Foulds, A. Fenwick, N. Hallowell, and A. Lucassen. 2013. Genetic medicine and incidental findings: It is more complicated than deciding whether to disclose or not. Genetics in Medicine 15: 896–899. Dorschner, M. O., L. M. Amendola, E. H. Turner, et al. 2013. Actionable, pathogenic incidental findings in 1,000 participants’ exomes. American Journal of Human Genetics 93(4): 631–640.
March, Volume 14, Number 3, 2014
Genetic Testing and Sequencing of Children
May, T., K. L. Zusevics, and K. A. Strong. 2013. On the ethics of clinical whole genome sequencing of children. Pediatrics. Epub ahead of print. doi: 10.1542/peds.2012-3788. Rhodes, R. 2006. Why test children for adult-onset genetic diseases? Mount Sinai Journal of Medicine 73:609–616.
Schotsmans, P. 1999. Personalism in medical ethics. Ethical Perspectives 6(1): 10–20. Wilson, J. 2005. To know or not to know? Genetic ignorance, autonomy and paternalism. Bioethics 19:492–504.
Downloaded by [University of Louisville] at 23:06 04 February 2015
Sapp, J. C., D. Dong, C. Stark, et al. 2013. Parental attitudes, values, and beliefs toward the return of results from exome se-
quencing in children. Clinical Genetics. Epub ahead of print. doi: 10.1111/cge.12254.
March, Volume 14, Number 3, 2014
ajob 33
